The present invention relates to cosmetics, particularly fragrances, which contain human pheromones. Pheromones are biochemicals produced by an animal or individual which elicits a specific physiological or behavioral response in another member of the same species. Different pheromones are produced by the members of each sex and received by specialized receptors in the nasal passage of members of the opposite sex. The human pheromones referred to in this invention are certain 16-Androstene and/or Estrene steroids, some of which occur naturally in humans.
16-Androstene steroids are structurally related to testosterone, and are characterized by the elimination of the 17-hydroxyl of testosterone to a 16-ene moiety. Some members of this group have been reported to act as pheromones in some mammalian species--for instance, 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497-502). These 16-Androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675).
Some studies have noted that, in some species, various characteristics of certain 16-Androstenes (including 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one), such as blood concentration, metabolism, and localization, are sexually dimorphic (Brooksbank, et al., J. Endocr. (1972) 52: 239-251; Claus, et al., J. Endocr. (1976) 68:483-484; Kwan, et al., Med. Sci. Res. (1987) 15:1443-1444). For instance, 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one, as well as 4,16-Androstadien-3-one, have been found at different concentrations in the peripheral blood, saliva and axillary secretions of men and of women (Kwan, T. K., et al., Med. Sci. Res. (1987) 15:1443-1444).
The possible function of some 16-Androstenes as human pheromones, to the extent of effecting choice and judgment, has been suggested (Id.; see also Gower, et al., "The Significance of Odorous Steroids in Axillary Odour", in, Perfumery, pgs 68-72, Van Toller and Dodd, Eds., Chapman and Hall, 1988); Kirk-Smith, D. A., et al., Res. Comm. Psychol. Psychiat. Behav. (1978) 3:379). Androstenol (5.alpha.-Androst-16-en-3.alpha.-ol) has been claimed to exhibit a pheromone-like activity in a commercial men's cologne and women's perfume (Andron.TM. for Men and Andron.TM. for Women by Jovan). Japanese Kokai patent, application No. 2295916, refers to perfume compositions containing androstenol and/or its analogue. 5,16-Androstadien-3.beta.-ol (and perhaps the 3.alpha.-ol) has also been identified in human axillary secretion (Gower, et al., Supra at 57-60.
Estrene steroids are typified by 17.beta.-Estradiol (1,3,5(10)-Estratrien-3,17.beta.-diol), and are characterized by a phenolic 1,3,5(10) A-ring and a hydroxy or hydroxy derivative, such as an ether or ester, at the 3-position. The pheromone properties of some estrene steroids for some mammalian species has been described. Michael, R. P. et al., Nature (1968) 218:746 refers to estrogens (particularly estradiol) as a pheromonal attractant of male rhesus monkeys. Parrot, R. F., Hormones and Behavior (1976) 7:207-215, reports estradiol benzoate injection induces mating behavior in ovariectomized rats; and the role of the blood level of estradiol in male sexual response (Phoenix, C. H., Physiol. and Behavior (1976) 16:305-310) and female sexual response (phoenix, C. H., Hormones and Behavior (1977) 8:356-362) in Rhesus monkeys has been described.
The human pheromones described in this application have been referred to previously in applicant's U.S. Ser. No. 07/707,862, filed May 5, 1991, U.S. Ser. No. 07/708,936, filed May 31, 1991, P.C.T. application No. PCT/US92/00219, filed Jan. 7, 1991, and P.C.T. application No. PCT/US92/00220 , filed Jan. 7, 1991, all of which are pending and are incorporated by reference.
The most likely means of communication of a putative human pheromone is the inhalation of a naturally occurring pheromone present on the skin of another. Several 16-Androstene steroids, including 5.alpha.-Androst-16-en-3.alpha.-ol and, 5.alpha.-Androst-16-en-3-one, 4,16-Androstadien-3-one, 5,16-Androstadien-3.alpha.-ol, and perhaps 5.alpha.-Androstadien-3.alpha.-ol, are naturally occurring in humans and may be present on the skin. It is estimated that the naturally occurring maximum concentration of all 16-Androstene steroids on human skin is from 2 to 7 ng/cm.sup.2. During intimate contact it is estimated that a human would be exposed to no more than 700 ng of a naturally occurring steroid. Since these compounds are relatively non-volatile, it is estimated that, even during intimate contact, a human subject would inhale no more than 0.7 pg of a naturally occurring steroid from the skin of another. The subject invention is effective because it delivers a much larger amount of the active pheromone steroids than does normal intimate contact between individuals.
There is however, little agreement in the literature as to whether or not any putative pheromone actually plays a role in the sexual or reproductive behavior of mammals, particularly of humans. See: Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", in: Mammalian Olfaction, Reproductive Processes, and Behavior, Doty, R. L., Ed., Academic Press, 1976. See also, Gower, et al., supra at 68-73.
Receptors for pheromones are found in the vomeronasal organ (VNO), a small structure which opens to the nasal passage in normal individuals (Moran, D. T., et al., J. Steroid Biochem. and Molec. Biol. (1991) 39:545; Stensaas, L. J., et al., J. Steroid Biochem. and Molec. Biol. (1991) 39:553; Garcia-Velasco, et al., J. Steroid Biochem. and Molec. Biol. (1991) 39:561). An odor does not bind to a VNO receptor--only a pheromone. A pheromone-specific change in the electrical potential of VNO receptor epithelium can be measured as described by Monti-Bloch, L., et al. (J. Steroid Biochem. and Molec. Biol. (1991) 39:573). This receptor binding activity is an essential characteristic of an active pheromone.
The compositions of many commercial perfumes and fragrances contain mammalian pheromones. Since pheromones are generally species specific, the mammalian pheromones found in commercial perfumes do not function as a pheromone, but instead provide a fixative note in the overall composition of the fragrance. Thus the perfumes, personal care products and cosmetics now available do not bind to pheromone receptors in the VNO and do not stimulate the vomeronasal nerve which communicates with the hypothalamus of the brain. Furthermore, in some cases the use of animal pheromones, or synthetics related to animal pheromones, may cause skin irritations or allergic responses in some individuals. Still further, since the source of animal pheromones used in fragrances are the anal glands of the contributing animal some individuals find it objectionable to use these substances. Finally, since none of the major ingredients found in commercial fragrances occur naturally on the human skin, the resulting scents are not natural human scents.
It would be preferable for a fragrance to contain naturally occurring human pheromones since this would result in stimulation of both olfactory (scent) receptors and pheromone receptors, would reduce the likelihood of irritation or an allergic response, would provide a more attractive composition for personal application, and would have a more natural human scent.